Altered aortic prostaglandin synthesis in a mild form of diabetes and the influence of dietary cholesterol.

Extreme hyperglycemia (350 mg/dl) in rats results from streptozocin injection (50 mg/kg) and leads to a reduced aortic capacity for prostacyclin synthesis. Other complications such as hyperlipemia and alterations in body weight gain (loss or no gain) that might be responsible for the altered aortic prostacyclin synthesis occur concurrently. We injected neonatal rats (2 days of age) with intraperitoneal streptozocin to induce chronic mild diabetes (mean plasma glucose, 241 mg/dl) characterized in adult rats by normal body weight gain, normolipemia, and a physical appearance virtually indistinguishable from controls. Plasma insulin levels were reduced in rats with mild diabetes rats to 66% of control levels. A group of control and diabetic rats were given a 0.5% cholesterol diet for 7 weeks to induce hyperlipemia. Rats with diabetes and control rats given the cholesterol diet had elevated plasma insulin levels of 32% and 51%, respectively, and no alteration in plasma glucose levels (compared with respective controls), suggesting a state of insulin resistance. Aortic synthesis of 6-keto-PGF1 alpha from endogenous arachidonic acid was reduced in rats with mild diabetes and normolipemia or hyperlipemia. In contrast, the aortic conversion of exogenous arachidonic acid to 6-keto-PGF1 alpha was reduced only in rats with mild diabetes and hyperlipemia. Our results demonstrate that: (1) aortic prostacyclin synthesis is reduced in mild diabetes in the absence of alteration in plasma lipid levels and body weight gain; (2) aortic prostacyclin synthesis from endogenous arachidonic acid is more sensitive to diabetes than synthesis from exogenous arachidonic acid; (3) dietary cholesterol induces a state similar to insulin resistance and interacts with mild diabetes, resulting in reduced aortic prostacyclin synthesis from exogenous arachidonic acid.